Effects of dietary carotenoids on mouse lung genomic profiles and their modulatory effects on short-term cigarette smoke exposures

Male C57BL/6 mice were fed diets supplemented with either β-carotene (BC) or lycopene (LY) that were formulated for human consumption. Four weeks of dietary supplementations results in plasma and lung carotenoid (CAR) concentrations that approximated the levels detected in humans. Bioactivity of the CARs was determined by assaying their effects on the activity of the lung transcriptome (~8,500 mRNAs). Both CARs activated the cytochrome P450 1A1 gene but only BC induced the retinol dehydrogenase gene. The contrasting effects of the two CARs on the lung transcriptome were further uncovered in mice exposed to cigarette smoke (CS) for 3 days; only LY activated ~50 genes detected in the lungs of CS-exposed mice. These genes encoded inflammatory-immune proteins. Our data suggest that mice offer a viable in vivo model for studying bioactivities of dietary CARs and their modulatory effects on lung genomic expression in both health and after exposure to CS toxicants

Ozone exposure activates oxidative stress responses in murine skin.

Ozone (O(3)) is among the most reactive environmental oxidant to which skin is exposed. O(3) exposure has previously been shown to induce antioxidant depletion as well as lipid and protein oxidation in the outermost skin layer, the stratum corneum (SC), but little is known regarding the potential effects of O(3) on the skin epidermis and dermis. To evaluate such skin responses to O(3), SKH-1 hairless mice were exposed for 2 h to 8.0 ppm O(3) or to ambient air. O(3) exposure caused a significant increase in skin carbonyls (28%) compared to the skin of air exposed control animals. An evident increase in 4-hydroxynonenal-protein adducts was detected after O(3) exposure. O(3) exposure caused a rapid up-regulation of HSP27 (20-fold), and more delayed induction of HSP70 (2.8-fold) and heme oxygenase-1 (5-fold). O(3) exposure also led to the induction of nitric oxide synthase (iNOS) 6-12 h following O(3) exposure. We conclude that skin exposure to high levels of O(3) not only affects antioxidant levels and oxidation markers in the SC, but also induces stress responses in the active layers of the skin, most likely by indirect mechanisms, since it is unlikely that O(3) itself penetrates the protective SC layers

Prostate cells exposed to lycopene in vitro liberate lycopene-enriched exosomes

OBJECTIVES: To investigate whether cellular exosomes liberated by prostatic cell lines in culture might be acting as the transport vehicles for the dietary antioxidant lycopene, known to be sequestered in the prostate gland and to reduce the risk of developing benign prostatic hyperplasia (BPH) and prostate cancer; its subsequent secretion into seminal plasma also confers protection to spermatozoa against oxidative free-radical damage.MATERIALS AND METHODS: Using benign and malignant human prostatic cell culture models, we assessed the role that their exosomes (the putative in vitro analogues of prostasomes) might have in the transport of lycopene.RESULTS: Cells exposed to lycopene in vitro accumulated the molecule and secrete lycopene-enriched exosomes. This continued after the lycopene exposure was stopped. Extraction of lycopene from the exosomes, followed by high-performance liquid chromatography, confirmed nanogram quantities of lycopene per milligram of exosomal protein. Packaging into exosomes for export resulted in reduced degradation of this labile antioxidant, and therefore maximized the effectiveness of delivery to the sites of action.CONCLUSION: These results support the likelihood that these organelles act as the transport vehicles for this important lipophilic agent known to have a role in the chemoprevention of various urological pathologies such as BPH, prostate cancer and male infertility.<br/

Lycopene inhibits DNA synthesis in primary prostate epithelial cells in vitro and its administration is associated with a reduced prostate-specific antigen velocity in a phase II clinical study.

Interest in lycopene has focused primarily on its use in the chemoprevention of prostate cancer (CaP); there are few clinical trials involving men with established disease. In addition, most data examining its mechanism of action have been obtained from experiments using immortal cell lines. We report the inhibitory effect(s) of lycopene in primary prostate epithelial cell (PEC) cultures, and the results of a pilot phase II clinical study investigating whole-tomato lycopene supplementation on the behavior of established CaP, demonstrating a significant and maintained effect on prostate-specific antigen velocity over 1 year. These data reinforce the justification for a large, randomized, placebo-controlled study